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  • 1
    Online Resource
    Online Resource
    Fibroblast Growth Factor-21 Is Induced in Human Skeletal Muscles by Hyperinsulinemia
    American Diabetes Association ; 2009
    In:  Diabetes Vol. 58, No. 12 ( 2009-12-01), p. 2797-2801
    Details
    In: Diabetes, American Diabetes Association, Vol. 58, No. 12 ( 2009-12-01), p. 2797-2801
    Abstract: Fibroblast growth factor-21 (FGF-21) is a potent metabolic regulator, which in animal models has been shown to improve glucose metabolism and insulin sensitivity. Recently, FGF-21 was shown to be expressed and secreted from murine muscle cells in response to insulin stimulation. RESEARCH DESIGN AND METHODS We studied muscular FGF-21 expression and plasma FGF-21 after acute insulin stimulation in young healthy men during a hyperinsulinemic- euglycemic clamp. Furthermore, we investigated systemic levels and muscle FGF-21 expression in humans with or without insulin resistance and chronic elevated insulin. RESULTS FGF-21 was barely detectable in young healthy men before insulin infusion. After 3 or 4 h of insulin infusion during a hyperinsulinemic-euglycemic clamp, muscular FGF-21 expression increased significantly. Plasma FGF-21 followed the same pattern. In individuals with chronic elevated insulin, muscular FGF-21 expression was associated with hyperinsulinemia in men but not in women. In plasma, hyperinsulinemia and fasting glucose were positively associated with plasma FGF-21 while plasma FGF-21 correlated negatively with HDL cholesterol. No associations between muscle and plasma FGF-21 were found in the individuals with chronic hyperinsulinemia. CONCLUSIONS FGF-21 is expressed in human skeletal muscle in response to insulin stimulation, suggesting that FGF-21 is an insulin-regulated myokine. In support, we found an association between chronic hyperinsulinemia and levels of FGF-21.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db09-0713
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2009
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    detail.hit.zdb_id: 1501252-9
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  • 2
    Online Resource
    Online Resource
    Long-term Cognitive Implications of Intrauterine Hyperglycemia in Adolescent Offspring of Women With Type 1 Diabetes (the EPICOM Study)
    American Diabetes Association ; 2016
    In:  Diabetes Care Vol. 39, No. 8 ( 2016-08-01), p. 1356-1363
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 39, No. 8 ( 2016-08-01), p. 1356-1363
    Abstract: Exposure to maternal diabetes in utero may have a negative impact on the developing brain. The objective was to examine long-term cognitive consequences of intrauterine hyperglycemia in adolescent offspring of women with type 1 diabetes and to ascertain a possible association with maternal HbA1c. RESEARCH DESIGN AND METHODS Offspring of a prospectively followed cohort of women with type 1 diabetes (n = 277) participated in a follow-up examination at the age of 13–19 years. A control group from the background population was identified (n = 301). Cognitive function was evaluated using Reynolds Intellectual Assessment Scales and classified into indices of composite intelligence, verbal and nonverbal intelligence, and composite memory. Frequencies of reading and writing problems and attendance to classes for children with learning difficulties were assessed. RESULTS Offspring of women with type 1 diabetes scored lower in all normalized and standardized intelligence indices compared with controls: composite intelligence (95.7 vs. 100, P = 0.001), verbal intelligence (96.2 vs. 100, P = 0.004), nonverbal intelligence (96.4 vs. 100, P = 0.008), and composite memory (95.7 vs. 100, P = 0.001). A higher frequency of diabetes-exposed offspring had parent-reported learning difficulties in primary school. Differences between groups remained after adjustment for confounders and potential mediators. We found no direct association between maternal HbA1c and offspring cognitive function in the exposed group. CONCLUSIONS Adolescent offspring of women with type 1 diabetes had lower cognitive function compared with a control group, also after adjustment for confounders and potential mediators. These differences may reflect direct harmful effects of maternal diabetes on neurodevelopment in the offspring.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc16-0168
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2016
    detail.hit.zdb_id: 1490520-6
    detail.hit.zdb_id: 441231-X
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  • 3
    Online Resource
    Online Resource
    Fatty Liver Among Adolescent Offspring of Women With Type 1 Diabetes (the EPICOM Study)
    American Diabetes Association ; 2019
    In:  Diabetes Care Vol. 42, No. 8 ( 2019-08-01), p. 1560-1568
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 42, No. 8 ( 2019-08-01), p. 1560-1568
    Abstract: Intrauterine exposure to maternal type 1 diabetes is associated with a less favorable metabolic profile later in life. Nonalcoholic fatty liver disease is the hepatic manifestation of a cluster of metabolic abnormalities linked to insulin resistance. This study aimed to evaluate the effect of maternal pregestational type 1 diabetes on the presence of fatty liver in offspring and the association between maternal BMI, glycemic control during pregnancy, offspring metabolic risk factors, and offspring level of soluble CD163 (sCD163) (a marker of macrophage activation) and risk of fatty liver. RESEARCH DESIGN AND METHODS This study was a prospective nationwide follow-up study of offspring (n = 278) of mothers with pregestational type 1 diabetes between 1993 and 1999 and matched control subjects (n = 303). Mean age at the time of follow-up was 16.7 years (range 13.0–20.4 years). We used the fatty liver index (FLI) and waist-to-height ratio (WHtR) to evaluate the presence of fatty liver among the offspring. An FLI ≥60 or WHtR & gt;0.469 were used as cutoff points for fatty liver. RESULTS More type 1 diabetes–exposed offspring had high FLI and WHtR indices compared with unexposed control subjects. We found significant associations between increasing maternal prepregnancy BMI, being born large for gestational age, offspring level of sCD163, as well as offspring metabolic risk factors (decreasing adiponectin and HDL cholesterol and increasing leptin, HOMA of insulin resistance, and HOMA of insulin secretion) and degree of fatty liver. CONCLUSIONS Intrauterine exposure to maternal type 1 diabetes and higher maternal prepregnancy BMI may predispose to fatty liver in the offspring. Offspring metabolic risk factors, including sCD163 levels, are associated with indices of fatty liver.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc19-0571
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
    detail.hit.zdb_id: 1490520-6
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  • 4
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    Online Resource
    Plasma YKL-40
    American Diabetes Association ; 2008
    In:  Diabetes Vol. 57, No. 11 ( 2008-11-01), p. 3078-3082
    Details
    In: Diabetes, American Diabetes Association, Vol. 57, No. 11 ( 2008-11-01), p. 3078-3082
    Abstract: OBJECTIVE—YKL-40 is produced by macrophages, and plasma YKL-40 is elevated in patients with diseases characterized by inflammation. In the present study, YKL-40 was examined in relation to obesity, inflammation, and type 2 diabetes. RESEARCH DESIGN AND METHODS—Plasma YKL-40 and adipose tissue YKL-40 mRNA levels were investigated in 199 subjects who were divided into four groups depending on the presence or absence of type 2 diabetes and obesity. In addition, plasma YKL-40 was examined in healthy subjects during a hyperglycemic clamp, in which the plasma glucose level was kept at 15 mmol/l for 3 h, and during a hyperinsulinemic-euglycemic clamp. RESULTS—Patients with type 2 diabetes had higher plasma YKL-40 (76.7 vs. 45.1 ng/ml, P = 0.0001) but not higher expression in adipose tissue YKL-40 mRNA (1.20 vs. 0.98, P = 0.2) compared with subjects with a normal glucose tolerance. Within the groups with normal glucose tolerance and type 2 diabetes, obesity subgroups showed no difference with respect to either plasma YKL-40 or adipose tissue YKL-40 mRNA levels. Multivariate regression analysis showed that plasma YKL-40 was associated with fasting plasma glucose (β = 0.5, P = 0.0014) and plasma interleukin (IL)-6 (β = 0.2, P = 0.0303). Plasma YKL-40 was not related to parameters of obesity. There were no changes in plasma YKL-40 in healthy subjects during either hyperglycemic or hyperinsulinemic-euglycemic clamps. CONCLUSIONS—Plasma YKL-40 was identified as an obesity-independent marker of type 2 diabetes related to fasting plasma glucose and plasma IL-6 levels.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db08-0182
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2008
    detail.hit.zdb_id: 80085-5
    detail.hit.zdb_id: 1501252-9
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  • 5
    Online Resource
    Online Resource
    Multisystem Morbidity and Mortality in Offspring of Women With Type 1 Diabetes (the EPICOM Study): A Register-Based Prospective Cohort Study
    American Diabetes Association ; 2015
    In:  Diabetes Care Vol. 38, No. 5 ( 2015-05-01), p. 821-826
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 38, No. 5 ( 2015-05-01), p. 821-826
    Abstract: This study examined the long-term consequences for offspring born to mothers with pregestational type 1 diabetes regarding mortality, hospital admissions, and medication. We also examined the association between HbA1c levels during pregnancy and mortality and incidence of hospital admissions. RESEARCH DESIGN AND METHODS We performed a prospective combined clinical and register-based cohort study comparing mortality, hospital admissions, and use of medication in offspring (n = 1,326) of women with pregestational type 1 diabetes (index children) with matched control subjects (n = 131,884). We also examined the association between HbA1c levels during pregnancy and mortality and the incidence of hospital admissions. Participants were monitored from birth to the age of 13–21 years. RESULTS Overall mortality was significantly increased for index children (hazard ratio 2.10, 95% CI 1.33–3.30, P = 0.001). The incidence of hospital admissions for index children was significantly increased (incidence rate ratio [IRR] 1.45, 95% CI 1.38–1.53, P & lt; 0.001), and this was the case for all age groups until the age of 15 years. The incidence of hospital admissions among index children was positively associated with maternal HbA1c before pregnancy and in the first trimester. In addition, the overall use of medication was increased in index children (IRR 1.13, 95% CI 1.07–1.19, P & lt; 0.001). CONCLUSIONS Type 1 diabetes during pregnancy has long-term implications on the health of offspring, with increased mortality, incidence of hospital admissions, and use of medication. Among mothers with type 1 diabetes, glycemic regulation is positively associated with incidence of hospital admissions in offspring.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc14-2907
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2015
    detail.hit.zdb_id: 1490520-6
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  • 6
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    Online Resource
    Prediction of Nonsevere Hypoglycemia—The Influence of Glycemic Variability in the HypoAna Study
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Introduction: In the struggle for tight glycemic control many type 1 diabetes patients daily experience large blood glucose fluctuations. It has been demonstrated that increased glucose variability is a predictor of hypoglycemia, which is the main limiting factor for achieving the recommended HbA1c target. The relationship between glucose variability and hypoglycemia might seem intuitive, but the exact nature of the relationship is difficult to elucidate. In this study we wanted to clarify the relationship between occurrence of non-severe hypoglycemia and glycemic variability in type 1 diabetic patients at high risk of severe hypoglycemia. Material and Methods: 72 patients participated for 4 x 3 days of blinded CGM recordings during a 2-year randomized balanced cross-over study with human insulins (regular/NPH) and insulin analogs (aspart/detemir). CGM recordings were used to calculate the coefficient of variation (CV) in glucose. Results: Treatment with insulin analogs resulted in a significant lower nocturnal CV (mean 29.2%, SD 9.1) than treatment with human insulin (mean 36.9%, SD 9.1) (p & lt;0.0001). CV was a significant risk marker of nocturnal asymptomatic hypoglycemia ?3.9 mmol/l in a multivariate analysis. A 1% increase in CV corresponds to a 5% (p & lt;0.0001) increase in asymptomatic hypoglycemia. CV did not predict hypoglycemia during daytime at this threshold. Conclusion: Treatment with insulin analogs provides less glycemic variability during night-time. The coefficient of variation in patients suffering from recurrent severe hypoglycemia predicts the occurrence of especially nocturnal hypoglycemia. Disclosure R.M. Agesen: None. P.L. Kristensen: Other Relationship; Self; Eli Lilly and Company. H. Beck-Nielsen: None. K. Nørgaard: Research Support; Self; Roche Diabetes Care Health and Digital Solutions. Advisory Panel; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic, Zealand Pharma A/S, Novo Nordisk A/S. Research Support; Self; Zealand Pharma A/S. T. Jensen: Stock/Shareholder; Self; Novo Nordisk A/S. B. Thorsteinsson: None. L. Tarnow: Stock/Shareholder; Self; Novo Nordisk A/S. U. Pedersen-Bjergaard: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Sanofi-Aventis. Consultant; Self; Medtronic.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-105-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 80085-5
    detail.hit.zdb_id: 1501252-9
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  • 7
    Online Resource
    Online Resource
    Fatty Liver Disease among Adolescent Offspring Born to Women with Pregestational Type 1 Diabetes (The EPICOM Study)
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Intrauterine exposure to maternal type 1 diabetes (T1DM) is associated with a less favourable metabolic profile later in life. Fatty liver disease can be considered as the hepatic manifestation of the cluster of metabolic abnormalities linked to insulin resistance. This study aimed to evaluate the effect of maternal pregestational T1DM on the offspring’s risk of fatty liver disease and any association between maternal glycemic control during pregnancy and later risk of fatty liver disease in the offspring. The study is a prospective nationwide follow-up study including offspring (n=277) born to mothers with pregestational T1DM between 1993-1999 and matched un-exposed controls (n=303). Age at the time of follow-up was 16.7 years (range 13.0-20.4 years). We used the Fatty Liver Index (FLI) and Waist-to-Height ratio (WHtR) to evaluate risk of fatty liver disease among the offspring. A FLI & gt;60 or a WHtR & gt;0.469 were used as indicators of fatty liver disease. Results are displayed in Table 1. More diabetes exposed offspring had high FLI and WHtR indices compared to un-exposed controls. Adjustment for maternal prepregnancy BMI, gender, age, and pubertal stage did not change overall results. No association between maternal glycemic control during pregnancy and risk of fatty liver disease was found.Table 1: Comparison of indicators of fatty liver disease among offspring born to mothers with T1DM.nExposedControlsp-value(n=277)(n=303)FLI & lt; 30495229 (46)266 (54)FLI & gt;30 & lt; 602518 (72)7 (28)FLI & gt;60149 (64)5 (36)0.02*WHtR  & lt;0.469489213 (44)276 (56)WHtR & gt;0.4699164 (70)27 (30) & lt;0.001*Data are displayed as numbers and percent.* Pearsons chi-squared test. FLI & lt;30 rules out and FLI & gt;60 as well as well as a WHtR & gt;0.469 rules in fatty liver disease. Conclusion: Intrauterine exposure to maternal T1DM may predispose to fatty liver disease. Disclosure S. Knorr: None. B. Bytoft: None. Z. Lohse: None. T.D. Clausen: None. R.B. Jensen: None. P. Damm: Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. H. Beck-Nielsen: None. C.H. Gravholt: None. D.M. Jensen: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-1444-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 80085-5
    detail.hit.zdb_id: 1501252-9
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